Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Drawings
The drawings are objected to because figure 25 is not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-15 and 18, 21) in the reply filed on 7/1/25 is acknowledged.
Claims 20 and 25 are withdrawn as being drawn to a non-elected invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-6, 9, 11, 14, 15, and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,928,389 (hereinafter “the reference patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 8 of the reference patent, even while reciting a method, also recites a device encompassed by the present claim 1. Examiner notes that “four separate lines of capture antibodies arranged parallel to one another and in a serpentine-like pattern”, recited by claim 1 of the reference patent, is equivalent to “parallel lines forming a barcoded pattern” recited by claim 1 of the present application.
As to the present claims 2-3, claim 1 of the reference patent recites that antibodies of adjacent lines of capture antibodies are configured to bind to a different target molecule.
As to the present claims 4-5, see claim 1 of the reference patent, which inherently meets the
present claims 4 and 5. Alternatively, see claim 16 of the reference patent.
As to the present claim 6, Examiner notes that the recitation of how the parallel lines are formed (by a microfluidic device) relates to a method of manufacturing the array. If the prior art device meets the array, then the prior art meets the claim, which is the case here (see discussion of the present claim 1 above).
As to the present claims 9, 11, 14, 15, and 21, see discussion of the present claim 1 above.
Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. U.S. Patent No. 10,928,389 (hereinafter “the reference patent”) in view of US 20040191124 (hereinafter “Noetzel”).
The reference patent, discussed above, is silent as to a separating unit for separating a fluidic component of fluid, the separating unit comprising a flowing microfluidic channel in fluid communication with an inlet and having a flow channel resistance, and an assaying microfluidic channel in fluid communication with the flowing channel and having an assaying channel resistance, wherein the flowing microfluidic channel resistance and the assaying microfluidic channel resistance are adapted to control flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel and wherein the array is located on the assaying microfluidic [channel].
However Noetzel discloses the following.
“The invention concerns an analytical test element for blood analyses especially by means of a single-use rapid test comprising a substrate body having a preferably microfluidic channel structure for the flow transport of a blood sample from an application site to at least one analytical site. The
invention also concerns a corresponding method for carrying out blood analyses in which a blood sample is conveyed by means of a channel structure in an analytical test element from an application site to at least one analytical site.” Paragraph 002 (emphasis added).
“A test element of this type is known from WO 01/24931. This application describes a channel or flow structure that is specially designed for separating plasma or serum from a whole blood sample and comprises two capillary-active zones where a first zone is composed of a porous matrix material and a second zone which is in contact with the first zone comprises one or more capillary channels. As a result the plasma obtained in the first zone is made available in the second zone free from interfering components as a target fluid for example for glucose tests.” Paragraph 003 (emphasis added).
It would have been obvious to one of ordinary skills in the art to provide in the invention of the reference patent a channel or flow structure for separating plasma or serum from a whole blood sample in a first zone so that plasma obtained in the first zone is made available in a second zone free from interfering components as a target fluid, as suggested by Noetzel. In such modification, the Noetzel detecting channel with adsorbed molecules (equivalent to the claimed assaying microfluidic channel) would be in the second zone for detection free from interfering components and in fluid communication with the channel for separating plasma or serum from whole blood taught by Noetzel (equivalent to the claimed flowing microfluidic channel). The porous matrix material (taught by Noetzel) is equivalent to the claimed flowing channel resistance. Alternatively, the channel wall or surface of the channel for separating plasma or serum from whole blood is considered equivalent to the claimed flowing channel resistance, since it provides a resistance to flow, and controls flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel. Likewise, the channel wall or surface of the Nicolau detecting channel with adsorbed molecules is considered equivalent to the claimed assaying channel resistance. Moreover, providing an inlet in fluid communication with the flowing microfluidic channel would have been obvious to one skilled in the art since it is predictable that it would provide the benefit of providing materials (such as a whole blood sample) to the channels discussed above.
Claims 7, 8, 12, 13, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. U.S. Patent No. 10,928,389 (hereinafter “the reference patent”) as applied to claim 1 above, in view of US 20020146745 (hereinafter “Natan”).
The reference patent, discussed above, does not recite the following limitations encompassed by claims 7, 8, 12, 13, and 18: the capture agents comprising a substrate polynucleotide attached to a substrate and a polynucleotide encoded protein hybridized to the substrate polynucleotide, wherein the substrate polynucleotides attached in the same substantially parallel line are the same, and the substrate polynucleotides attached in each substantially parallel line forming the barcode pattern are different relative to the substrate polynucleotides attached to adjacent lines of the substantially parallel lines forming the barcode pattern
Examiner notes that the reference patent recites a plurality of isolated features, that each isolated feature has different types of antibodies, i.e., antibodies that binding different proteins of interest, and that the isolated features form parallel lines with respect to each other (which thus is equivalent to a barcode pattern). However, the reference patent is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a nucleotide attached to the capture antibody.
Natan however discloses this type of immobilization of antibodies as follows.
“When the present invention is used for multiplexed assays, the full set of capture probes contains a variety of binding moieties and a variety of pairing oligonucleotides. Unique pairs of binding moieties and pairing oligonucleotides are found on each type of capture probe, ensuring that only one type of binding moiety is targeted to an array region containing a particular capture oligonucleotide.” Para. 0032 (emphasis added).
“Binding moieties of the present invention include any moiety capable of binding to an analyte with any degree of affinity and specificity. There is essentially no limitation on the type and number of potential binding moieties that can be used in the capture probes of the present invention. Examples of binding moieties and analytes include enzymes and substrates, antibodies and epitopes, carbohydrates and lectins, receptors and ligands, and nucleic acids and complementary nucleic acids, among others Thus, binding moieties include, but are not limited to, proteins, peptides, enzymes, enzyme substrates, antibodies, antibody fragments, oligonucleotides (single-, double-, or triple-stranded DNA or RNA), oligosaccharides, hormones, opiates, steroids, hormone receptors, carbohydrates, cofactors, drugs, lectins, sugars, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, and small molecules that can bind receptors or inhibit enzymes.” Para. 0033 (emphasis added).
“Binding moieties range in their affinity and specificity for analytes. High-specificity binding moieties such as protein-specific antibodies are employed in assays for particular analytes, e.g., diagnostic assays for proteins known to be markers for a particular disease. Hundreds of monoclonal and polyclonal antibodies are available commercially. Examples include antibodies to CD antigens and their receptors, histocompatibility antigens, immunoglobulin, matrix metalloproteinases and their inhibitors, and acute phase proteins. Note that antibodies can capture not only free analytes but also, in some cases, analytes with bound receptor or autoantibody.” Para. 0034 (emphasis added).
“Capture probes can be constructed from any type of particle such as a latex bead. Preferably, the particles are cylindrically-shaped, segmented metal nanoparticles, as shown in FIG. 3. Suitable metals include, without limitation, gold, platinum, nickel, copper, silver, palladium, cobalt, rhodium, and iridium. The particles can also be made of a metal chalcogenide, oxide, sulfide, nitride, phosphide, selenide, telluride, or antimonide, a metal alloy, a semiconductor or semi-metal, an organic or organometallic compound or material, or a particulate or composite material. A nanoparticle 50 has all dimensions less than approximately 100 nm and contains at least two, and preferably at least three, different segments (or "stripes") having different surface compositions. Preferred particle dimensions are between approximately 70 and 100 nm in length and between approximately 10 and 50 nm in diameter. The different surface compositions facilitate attachment and localization of the binding moieties and the pairing oligonucleotides to different regions of the surface. In FIG. 3, the binding moieties are fixed to an inner region 52, and the pairing oligonucleotides to outer regions 54 and 56. Although it is preferred that the binding moieties and pairing oligonucleotides remain in separate regions to prevent the binding moieties and captured analytes from sterically interfering with oligonucleotide hybridization, it is not necessary. For the same reason, it is preferred that the outer regions 54 and 56 contain the pairing oligonucleotides, with the binding moieties localized to the inner region 52.” Para. 0044 (emphasis added).
“The particles of FIG. 3 are advantageous because their stripe pattern serves as a nanoscale barcode that can be used to encode the identity of the attached binding moieties and pairing oligonucleotides. This may be useful to confirm that the capture probes self-assemble to the correct locations or to identify the probes after they are removed from the array. In this case, each type of capture probe contains a different stripe pattern…” Para. 0049 (emphasis added).
“Arrays containing position-addressable surface-bound capture oligonucleotides are available commercially or can be prepared using methods known in the art. Preferably, the arrays are produced through spatially-directed oligonucleotide synthesis, which includes any method of directing the synthesis of an oligonucleotide to a specific location on a substrate. Methods for spatially directed oligonucleotide synthesis include, without limitation, light-directed oligonucleotide synthesis, microlithography, application by ink jet, microchannel deposition to specific locations, and sequestration with physical barriers. In general, these methods involve generating active sites, usually by removing protective groups, and coupling to the active site a nucleotide that, itself, optionally has a protected active site if further nucleotide coupling is desired…” Para. 0061 (emphasis added).
Thus, while the reference patent is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a polynucleotide attached to the capture antibody, using this type of immobilization of the antibodies to the substrate would have been obvious in view of the teachings of Natan which discloses hybridization of substrate oligonucleotide to oligonucleotides attached to capture antibodies or proteins (para. See para. 0032 disclosing unique (i.e., different) pairs of binding moieties of capture probes and oligonucleotides for an array region, and see paras. 0033 and 0034 disclosing that the binding moieties can be proteins or antibodies). One skilled in the art would have had reasonable expectation of success given that Natan teaches that the capture antibody/protein can be bound on a substrate in a stripe pattern (para. 0049) using various known means (para. 0061).
Thus, the reference patent recites isolated features that form parallel lines (a barcode pattern), wherein each isolated feature (i.e., each line) has different types of antibodies (i.e., antibodies that binding different proteins of interest), and it would have been obvious to utilize substrate polynucleotides with polynucleotide-encoded protein (or polynucleotide-encoded antibody) as the particular means for immobilization of the protein or antibody, as taught by Natan.
Claims 1-6, 9, 11, 14, 15, and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. 10,274,486 (hereinafter “the reference patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 8 (which depends from 1) of the reference patent recites a device encompassed by the present claim 1. Examiner notes that “isolated features [containing immobilized antibodies] are arranged in parallel within the enclosed interfaces”, recited by claim 8 (which depends from claim 1) of the reference patent, is equivalent to “parallel lines forming a barcoded pattern” recited by claim 1 of the present application.
As to the present claims 2-3, claim 1 of the reference patent recites that antibodies of adjacent lines of capture antibodies are configured to bind to a different target molecule.
As to the present claims 4-5, see claim 1 of the reference patent, which inherently meets the
present claims 4 and 5. Alternatively, see claim 16 of the reference patent.
As to the present claim 6, Examiner notes that the recitation of how the parallel lines are formed (by a microfluidic device) relates to a method of manufacturing the array. If the prior art device meets the array, then the prior art meets the claim, which is the case here (see discussion of the present claim 1 above).
As to the present claims 9, 11, 14, 15, and 21, see discussion of the present claim 1 above.
Claim 10 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. U.S. Patent No. 10,274,486 (hereinafter “the reference patent”) in view of US 20040191124 (hereinafter “Noetzel”).
The reference patent, discussed above, is silent as to a separating unit for separating a fluidic component of fluid, the separating unit comprising a flowing microfluidic channel in fluid communication with an inlet and having a flow channel resistance, and an assaying microfluidic channel in fluid communication with the flowing channel and having an assaying channel resistance, wherein the flowing microfluidic channel resistance and the assaying microfluidic channel resistance are adapted to control flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel and wherein the array is located on the assaying microfluidic [channel].
However Noetzel discloses the following.
“The invention concerns an analytical test element for blood analyses especially by means of a single-use rapid test comprising a substrate body having a preferably microfluidic channel structure for the flow transport of a blood sample from an application site to at least one analytical site. The
invention also concerns a corresponding method for carrying out blood analyses in which a blood sample is conveyed by means of a channel structure in an analytical test element from an application site to at least one analytical site.” Paragraph 002 (emphasis added).
“A test element of this type is known from WO 01/24931. This application describes a channel or flow structure that is specially designed for separating plasma or serum from a whole blood sample and comprises two capillary-active zones where a first zone is composed of a porous matrix material and a second zone which is in contact with the first zone comprises one or more capillary channels. As a result the plasma obtained in the first zone is made available in the second zone free from interfering components as a target fluid for example for glucose tests.” Paragraph 003 (emphasis added).
It would have been obvious to one of ordinary skills in the art to provide in the invention of the reference patent a channel or flow structure for separating plasma or serum from a whole blood sample in a first zone so that plasma obtained in the first zone is made available in a second zone free from interfering components as a target fluid, as suggested by Noetzel. In such modification, the Noetzel detecting channel with adsorbed molecules (equivalent to the claimed assaying microfluidic channel) would be in the second zone for detection free from interfering components and in fluid communication with the channel for separating plasma or serum from whole blood taught by Noetzel (equivalent to the claimed flowing microfluidic channel). The porous matrix material (taught by Noetzel) is equivalent to the claimed flowing channel resistance. Alternatively, the channel wall or surface of the channel for separating plasma or serum from whole blood is considered equivalent to the claimed flowing channel resistance, since it provides a resistance to flow, and controls flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel. Likewise, the channel wall or surface of the Nicolau detecting channel with adsorbed molecules is considered equivalent to the claimed assaying channel resistance. Moreover, providing an inlet in fluid communication with the flowing microfluidic channel would have been obvious to one skilled in the art since it is predictable that it would provide the benefit of providing materials (such as a whole blood sample) to the channels discussed above.
Claims 7, 8, 12, 13, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of U.S. Patent No. U.S. Patent No. 10,274,486 (hereinafter “the reference patent”) as applied to claim 1 above, in view of US 20020146745 (hereinafter “Natan”).
The reference patent, discussed above, does not recite the following limitations encompassed by claims 7, 8, 12, 13, and 18: the capture agents comprising a substrate polynucleotide attached to a substrate and a polynucleotide encoded protein hybridized to the substrate polynucleotide, wherein the substrate polynucleotides attached in the same substantially parallel line are the same, and the substrate polynucleotides attached in each substantially parallel line forming the barcode pattern are different relative to the substrate polynucleotides attached to adjacent lines of the substantially parallel lines forming the barcode pattern
Examiner notes that the reference patent recites a plurality of isolated features, that each isolated feature has different types of antibodies, i.e., antibodies that binding different proteins of interest, and that the isolated features form parallel lines with respect to each other (which thus is equivalent to a barcode pattern). However, the reference patent is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a nucleotide attached to the capture antibody.
Natan however discloses this type of immobilization of antibodies as follows.
“When the present invention is used for multiplexed assays, the full set of capture probes contains a variety of binding moieties and a variety of pairing oligonucleotides. Unique pairs of binding moieties and pairing oligonucleotides are found on each type of capture probe, ensuring that only one type of binding moiety is targeted to an array region containing a particular capture oligonucleotide.” Para. 0032 (emphasis added).
“Binding moieties of the present invention include any moiety capable of binding to an analyte with any degree of affinity and specificity. There is essentially no limitation on the type and number of potential binding moieties that can be used in the capture probes of the present invention. Examples of binding moieties and analytes include enzymes and substrates, antibodies and epitopes, carbohydrates and lectins, receptors and ligands, and nucleic acids and complementary nucleic acids, among others Thus, binding moieties include, but are not limited to, proteins, peptides, enzymes, enzyme substrates, antibodies, antibody fragments, oligonucleotides (single-, double-, or triple-stranded DNA or RNA), oligosaccharides, hormones, opiates, steroids, hormone receptors, carbohydrates, cofactors, drugs, lectins, sugars, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, and small molecules that can bind receptors or inhibit enzymes.” Para. 0033 (emphasis added).
“Binding moieties range in their affinity and specificity for analytes. High-specificity binding moieties such as protein-specific antibodies are employed in assays for particular analytes, e.g., diagnostic assays for proteins known to be markers for a particular disease. Hundreds of monoclonal and polyclonal antibodies are available commercially. Examples include antibodies to CD antigens and their receptors, histocompatibility antigens, immunoglobulin, matrix metalloproteinases and their inhibitors, and acute phase proteins. Note that antibodies can capture not only free analytes but also, in some cases, analytes with bound receptor or autoantibody.” Para. 0034 (emphasis added).
“Capture probes can be constructed from any type of particle such as a latex bead. Preferably, the particles are cylindrically-shaped, segmented metal nanoparticles, as shown in FIG. 3. Suitable metals include, without limitation, gold, platinum, nickel, copper, silver, palladium, cobalt, rhodium, and iridium. The particles can also be made of a metal chalcogenide, oxide, sulfide, nitride, phosphide, selenide, telluride, or antimonide, a metal alloy, a semiconductor or semi-metal, an organic or organometallic compound or material, or a particulate or composite material. A nanoparticle 50 has all dimensions less than approximately 100 nm and contains at least two, and preferably at least three, different segments (or "stripes") having different surface compositions. Preferred particle dimensions are between approximately 70 and 100 nm in length and between approximately 10 and 50 nm in diameter. The different surface compositions facilitate attachment and localization of the binding moieties and the pairing oligonucleotides to different regions of the surface. In FIG. 3, the binding moieties are fixed to an inner region 52, and the pairing oligonucleotides to outer regions 54 and 56. Although it is preferred that the binding moieties and pairing oligonucleotides remain in separate regions to prevent the binding moieties and captured analytes from sterically interfering with oligonucleotide hybridization, it is not necessary. For the same reason, it is preferred that the outer regions 54 and 56 contain the pairing oligonucleotides, with the binding moieties localized to the inner region 52.” Para. 0044 (emphasis added).
“The particles of FIG. 3 are advantageous because their stripe pattern serves as a nanoscale barcode that can be used to encode the identity of the attached binding moieties and pairing oligonucleotides. This may be useful to confirm that the capture probes self-assemble to the correct locations or to identify the probes after they are removed from the array. In this case, each type of capture probe contains a different stripe pattern…” Para. 0049 (emphasis added).
“Arrays containing position-addressable surface-bound capture oligonucleotides are available commercially or can be prepared using methods known in the art. Preferably, the arrays are produced through spatially-directed oligonucleotide synthesis, which includes any method of directing the synthesis of an oligonucleotide to a specific location on a substrate. Methods for spatially directed oligonucleotide synthesis include, without limitation, light-directed oligonucleotide synthesis, microlithography, application by ink jet, microchannel deposition to specific locations, and sequestration with physical barriers. In general, these methods involve generating active sites, usually by removing protective groups, and coupling to the active site a nucleotide that, itself, optionally has a protected active site if further nucleotide coupling is desired…” Para. 0061 (emphasis added).
Thus, while the reference patent is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a polynucleotide attached to the capture antibody, using this type of immobilization of the antibodies to the substrate would have been obvious in view of the teachings of Natan which discloses hybridization of substrate oligonucleotide to oligonucleotides attached to capture antibodies or proteins (para. See para. 0032 disclosing unique (i.e., different) pairs of binding moieties of capture probes and oligonucleotides for an array region, and see paras. 0033 and 0034 disclosing that the binding moieties can be proteins or antibodies). One skilled in the art would have had reasonable expectation of success given that Natan teaches that the capture antibody/protein can be bound on a substrate in a stripe pattern (para. 0049) using various known means (para. 0061).
Thus, the reference patent recites isolated features that form parallel lines (a barcode pattern), wherein each isolated feature (i.e., each line) has different types of antibodies (i.e., antibodies that binding different proteins of interest), and it would have been obvious to utilize substrate polynucleotides with polynucleotide-encoded protein (or polynucleotide-encoded antibody) as the particular means for immobilization of the protein or antibody, as taught by Natan.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1-6, 9, 11, 14, 15, and 21 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by US 20040224321 (hereinafter “Nicolau”).
Nicolau discloses the following, which are considered relevant to Applicant’s claims.
“A further problem associated with the use of arrays is the identification of different samples within the array, or the identification of different test samples that are applied to the array in an assay.
Advantageously, at least one embodiment of the present invention provides an `informationally-addressable` structure or an array where information about each sample in the array or each test sample applied to the array in a assay is encoded by the combination of shallow-profiled features within the array.” Paragraph 0009 (emphasis added).
“In yet a further aspect of the invention there is provided an assay method comprising the steps of: (i) contacting an array described above with a test sample that may contain an analyte that binds to the at least one biomolecule adsorbed on the surface within the at least one profiled feature; (ii) detecting binding of the analyte and the adsorbed biomolecule.” Paragraphs 0017-0019.
“In a preferred embodiment, the structure includes an orderly arrangement of a plurality of profiled features. The plurality of profiled features may form a plurality of wells or a plurality of channels. In a particularly preferred embodiment, the plurality of profiled features may be arranged in a pattern that is capable of identifying a feature of an array formed from the structure. For example, a plurality of channels may be formed in a "bar code" type arrangement and each structure may contain a plurality of different bar code type arrangements. Each bar code type arrangement may be used to encode particular information about an array prepared from the structure or the samples applied to the array in an assay. The term "informationally-addressable" as used herein refers to the ability of the
profiled features to encode information about an array or an assay.” Paragraph 0037 (emphasis added).
“In one embodiment, each informationally-addressable profiled feature or bar code may be used to identify a different molecule adsorbed on the surface of the first layer in a profiled feature of an array or may be used to identify a series of different concentrations of a single molecule adsorbed on a respective series of bar code type arrangements. Alternatively, each bar code arrangement may be used to encode information about an assay in which the array is to be used. For example, the bar code may be used to identify the source of the analyte or recognition component. In a diagnostic assay where each profiled feature forms a bar code and each profiled feature has the same molecule, eg. a protein or gene, adsorbed on the exposed surface of the first layer, the bar code could be used to identify the patient who is being tested.” Paragraph 0038 (emphasis added).
“Linear structures which both decrease the actual amount of protein used for deposition, especially if a spatially-addressable deposition is used, as well as increase the capacity for miniaturization in a lateral if not in a 2D manner, were fabricated. Another benefit of this approach arises from the possibility to encode the information (e.g. type of antibody, concentration) through a combination of vertical lines in a `bar code`, `informationally-addressable` mode and not in a 2D, spatially-addressable mode like in the classical arrays. The results also demonstrate, inter alia, the
complexities of protein adsorption in fabricated channels, with the resolution of the variation of the protein concentration in the nanometer range. These complexities are likely to have an increasingly important impact in microfluidics, especially for devices that comprise nano-channels. Paragraph 0092 (emphasis added).
Thus as to Applicant’s claims 1, 9 and 21, Nicolau discloses an array for detecting at least one target in a sample [see para. 0038 disclosing “addressable profiled feature or bar code may be used to identify a different molecule adsorbed on the surface of the first layer in a profiled feature of an array”], the array comprising:
at least one capture agent or component thereof attached to a substrate [i.e., the molecule adsorbed on the layer, see para. 0038],
the at least one capture agent capable of specifically binding the at least one target to form a capture agent target binding complex [see paragraphs 0017-0019]
the at least one capture agent or component thereof arranged on the array so that capture agent target binding complexes are detectable [paragraphs 0017-0019] along substantially parallel lines forming a barcoded pattern [paragraphs 0037-0038 and 0092].
As to claims 2, 3, and 15, there is a plurality of targets and capture agents, wherein each capture agent is bindingly distinguishable [see paragraph 0038, which discloses different molecules adsorbed on the surface] and positionally distinguishable from another [see para. 0038 disclosing that a bar code may be used to identify a different molecule adsorbed on the surface], each capture agent capable of specifically binding each target [see paragraphs 0017-0019 which discloses detecting binding between an analyte and the molecule adsorbed on the surface].
As to claim 4, see paragraphs 0017-0019.
As to claim 5, see paragraph 0038.
As to claim 6, see paragraph 0037 of Nicolau disclosing that the profiled features may form a plurality of channels formed in a bar code. The channels are micro-channels (see the Nicolau abstract disclosing micro/nano-structures; and see channel dimensions in para. 0061.)
As to claim 11, Nicolau discloses that there is a plurality of targets and capture agents, wherein each capture agent is bindingly distinguishable [see paragraph 0038, which discloses different molecues adsorbed on the surface] and positionally distinguishable from another [see para. 0038 disclosing that a bar code may be used to identify a different molecule adsorbed on the surface], each capture agent capable of specifically binding each target [see paragraphs 0017-0019 which discloses detecting binding between an analyte and the molecule adsorbed on the surface].
As to claims 14, see the above discussion of claim 1 regarding the claimed array. As for the claimed device for detecting the barcoded pattern on the array, see paragraph 0047 disclosing use of fluorescence detection to detect the binding between analyte and adsorbed molecule.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claim 10 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 20040224321 (hereinafter “Nicolau”) in view of US 20040191124 (hereinafter “Noetzel”).
Nicolau, discussed above, is silent as to a separating unit for separating a fluidic component of fluid, the separating unit comprising a flowing microfluidic channel in fluid communication with an inlet and having a flow channel resistance, and an assaying microfluidic channel in fluid communication with the flowing channel and having an assaying channel resistance, wherein the flowing microfluidic channel resistance and the assaying microfluidic channel resistance are adapted to control flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel and wherein the array is located on the assaying microfluidic [channel].
However Noetzel discloses the following.
“The invention concerns an analytical test element for blood analyses especially by means of a single-use rapid test comprising a substrate body having a preferably microfluidic channel structure for the flow transport of a blood sample from an application site to at least one analytical site. The
invention also concerns a corresponding method for carrying out blood analyses in which a blood sample is conveyed by means of a channel structure in an analytical test element from an application site to at least one analytical site.” Paragraph 002 (emphasis added).
“A test element of this type is known from WO 01/24931. This application describes a channel or flow structure that is specially designed for separating plasma or serum from a whole blood sample and comprises two capillary-active zones where a first zone is composed of a porous matrix material and a second zone which is in contact with the first zone comprises one or more capillary channels. As a result the plasma obtained in the first zone is made available in the second zone free from interfering components as a target fluid for example for glucose tests.” Paragraph 003 (emphasis added).
It would have been obvious to one of ordinary skills in the art to provide in the Nicolau invention a channel or flow structure for separating plasma or serum from a whole blood sample in a first zone so that plasma obtained in the first zone is made available in a second zone free from interfering components as a target fluid, as suggested by Noetzel. In such modification, the Noetzel detecting channel with adsorbed molecules (equivalent to the claimed assaying microfluidic channel) would be in the second zone for detection free from interfering components and in fluid communication with the channel for separating plasma or serum from whole blood taught by Noetzel (equivalent to the claimed flowing microfluidic channel). The porous matrix material (taught by Noetzel) is equivalent to the claimed flowing channel resistance. Alternatively, the channel wall or surface of the channel for separating plasma or serum from whole blood is considered equivalent to the claimed flowing channel resistance, since it provides a resistance to flow, and controls flowing of the fluidic component from the flowing microfluidic channel to the assaying microfluidic channel. Likewise, the channel wall or surface of the Nicolau detecting channel with adsorbed molecules is considered equivalent to the claimed assaying channel resistance. Moreover, providing an inlet in fluid communication with the flowing microfluidic channel would have been obvious to one skilled in the art since it is predictable that it would provide the benefit of providing materials (such as a whole blood sample) to the channels discussed above.
Claims 7, 8, 12, 13, and 18 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over US 20040224321 (hereinafter “Nicolau”), as applied to claim 1 above, in view of US 20020146745 (hereinafter “Natan”).
Nicolau, discussed above, does not recite the following limitations encompassed by claims 7, 8, 12, 13, and 18: the capture agents comprising a substrate polynucleotide attached to a substrate and a polynucleotide encoded protein hybridized to the substrate polynucleotide, wherein the substrate polynucleotides attached in the same substantially parallel line are the same, and the substrate polynucleotides attached in each substantially parallel line forming the barcode pattern are different relative to the substrate polynucleotides attached to adjacent lines of the substantially parallel lines forming the barcode pattern
Examiner notes that the reference patent recites a plurality of isolated features, that each isolated feature has different types of antibodies, i.e., antibodies that binding different proteins of interest, and that the isolated features form parallel lines with respect to each other (which thus is equivalent to a barcode pattern). However, the reference patent is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a nucleotide attached to the capture antibody.
Natan however discloses this type of immobilization of antibodies as follows.
“When the present invention is used for multiplexed assays, the full set of capture probes contains a variety of binding moieties and a variety of pairing oligonucleotides. Unique pairs of binding moieties and pairing oligonucleotides are found on each type of capture probe, ensuring that only one type of binding moiety is targeted to an array region containing a particular capture oligonucleotide.” Para. 0032 (emphasis added).
“Binding moieties of the present invention include any moiety capable of binding to an analyte with any degree of affinity and specificity. There is essentially no limitation on the type and number of potential binding moieties that can be used in the capture probes of the present invention. Examples of binding moieties and analytes include enzymes and substrates, antibodies and epitopes, carbohydrates and lectins, receptors and ligands, and nucleic acids and complementary nucleic acids, among others Thus, binding moieties include, but are not limited to, proteins, peptides, enzymes, enzyme substrates, antibodies, antibody fragments, oligonucleotides (single-, double-, or triple-stranded DNA or RNA), oligosaccharides, hormones, opiates, steroids, hormone receptors, carbohydrates, cofactors, drugs, lectins, sugars, agonists and antagonists for cell membrane receptors, toxins and venoms, viral epitopes, and small molecules that can bind receptors or inhibit enzymes.” Para. 0033 (emphasis added).
“Binding moieties range in their affinity and specificity for analytes. High-specificity binding moieties such as protein-specific antibodies are employed in assays for particular analytes, e.g., diagnostic assays for proteins known to be markers for a particular disease. Hundreds of monoclonal and polyclonal antibodies are available commercially. Examples include antibodies to CD antigens and their receptors, histocompatibility antigens, immunoglobulin, matrix metalloproteinases and their inhibitors, and acute phase proteins. Note that antibodies can capture not only free analytes but also, in some cases, analytes with bound receptor or autoantibody.” Para. 0034 (emphasis added).
“Capture probes can be constructed from any type of particle such as a latex bead. Preferably, the particles are cylindrically-shaped, segmented metal nanoparticles, as shown in FIG. 3. Suitable metals include, without limitation, gold, platinum, nickel, copper, silver, palladium, cobalt, rhodium, and iridium. The particles can also be made of a metal chalcogenide, oxide, sulfide, nitride, phosphide, selenide, telluride, or antimonide, a metal alloy, a semiconductor or semi-metal, an organic or organometallic compound or material, or a particulate or composite material. A nanoparticle 50 has all dimensions less than approximately 100 nm and contains at least two, and preferably at least three, different segments (or "stripes") having different surface compositions. Preferred particle dimensions are between approximately 70 and 100 nm in length and between approximately 10 and 50 nm in diameter. The different surface compositions facilitate attachment and localization of the binding moieties and the pairing oligonucleotides to different regions of the surface. In FIG. 3, the binding moieties are fixed to an inner region 52, and the pairing oligonucleotides to outer regions 54 and 56. Although it is preferred that the binding moieties and pairing oligonucleotides remain in separate regions to prevent the binding moieties and captured analytes from sterically interfering with oligonucleotide hybridization, it is not necessary. For the same reason, it is preferred that the outer regions 54 and 56 contain the pairing oligonucleotides, with the binding moieties localized to the inner region 52.” Para. 0044 (emphasis added).
“The particles of FIG. 3 are advantageous because their stripe pattern serves as a nanoscale barcode that can be used to encode the identity of the attached binding moieties and pairing oligonucleotides. This may be useful to confirm that the capture probes self-assemble to the correct locations or to identify the probes after they are removed from the array. In this case, each type of capture probe contains a different stripe pattern…” Para. 0049 (emphasis added).
“Arrays containing position-addressable surface-bound capture oligonucleotides are available commercially or can be prepared using methods known in the art. Preferably, the arrays are produced through spatially-directed oligonucleotide synthesis, which includes any method of directing the synthesis of an oligonucleotide to a specific location on a substrate. Methods for spatially directed oligonucleotide synthesis include, without limitation, light-directed oligonucleotide synthesis, microlithography, application by ink jet, microchannel deposition to specific locations, and sequestration with physical barriers. In general, these methods involve generating active sites, usually by removing protective groups, and coupling to the active site a nucleotide that, itself, optionally has a protected active site if further nucleotide coupling is desired…” Para. 0061 (emphasis added).
Thus, while Nicolau is silent as to the different types of antibodies being bound to the substrate via hybridization of a substrate polynucleotide and a polynucleotide attached to the capture antibody, using this type of immobilization of the antibodies to the substrate would have been obvious in view of the teachings of Natan which discloses hybridization of substrate oligonucleotide to oligonucleotides attached to capture antibodies or proteins (para. See para. 0032 disclosing unique (i.e., different) pairs of binding moieties of capture probes and oligonucleotides for an array region, and see paras. 0033 and 0034 disclosing that the binding moieties can be proteins or